Rhinovirus infection in young children is associated with elevated airway TSLP levels

Pérez, Geovanny F.; Pancham, Krishna; Huseni, Shehlanoor; Preciado, Diego; Freishtat, Robert J.; Colberg-Poley, Anamaris M.; Hoffman, Eric P.; Rose, Mary C.; Niño, Gustavo

doi:10.1183/09031936.00049214

Cited by 45 publications

(43 citation statements)

References 15 publications

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“…This deficient Th1 cytokine production in neonates may explain the susceptibility of this age group to certain pathogens such as RSV and HMPV [20,21]. These findings are in agreement with previous reports of an unbalanced nasal airway Th1/Th2 response during RSV and RV infection in young children [22,23]. The effect of RV and RSV inducing Th2 airway immune responses has also been reported in animal models [24,25], including studies investigating viral-induced airway hyper-reactivity in neonatal mice [25].…”

Section: Discussionsupporting

confidence: 91%

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

et al. 2016

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Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks), 12% in preterm (32–37 weeks) and 21% in severely premature children (<32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.

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Section: Discussionsupporting

confidence: 91%

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

et al. 2016

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“…Viral infection with rhinovirus, human metapneumovirus and respiratory syncytial virus can induce TSLP expression in airway epithelial cells (9, 16, 17). In particular, rhinovirus infection has been found associated with TSLP levels in the airways of young children (18). Rhinovirus infection can induce IL33 secretion in human bronchial epithelial cells to promote Th2 inflammation and exacerbate asthma severity in patients (19).…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide Attenuates Induction of Proallergic Cytokines, Thymic Stromal Lymphopoietin, and Interleukin 33 in Respiratory Epithelial Cells Stimulated with PolyI:C and Human Parechovirus

Lin

Cheng

et al. 2016

Front. Immunol.

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Epidemiological studies based on the “hygiene hypothesis” declare that the level of childhood exposure to environmental microbial products is inversely related to the incidence of allergic diseases in later life. Multiple types of immune cell-mediated immune regulation networks support the hygiene hypothesis. Epithelial cells are the first line of response to microbial products in the environment and bridge the innate and adaptive immune systems; however, their role in the hygiene hypothesis is unknown. To demonstrate the hygiene hypothesis in airway epithelial cells, we examined the effect of lipopolysaccharide (LPS; toll-like receptor 4 ligand) on the expression of the proallergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL33) in H292 cells (pulmonary mucoepidermoid carcinoma cells). Stimulation with the TLR ligand polyI:C and human parechovirus type 1 (HPeV1) but not LPS-induced TSLP and IL33 through interferon regulatory factor 3 (IRF3) and NF-κB activity, which was further validated by using inhibitors (dexamethasone and Bay 11-7082) and short hairpin RNA-mediated gene knockdown. Importantly, polyI:C and HPeV1-stimulated TSLP and IL33 induction was reduced by LPS treatment by attenuating TANK-binding kinase 1, IRF3, and NF-κB activation. Interestingly, the basal mRNA levels of TLR signaling proteins were downregulated with long-term LPS treatment of H292 cells, which suggests that such long-term exposure modulates the expression of innate immunity signaling molecules in airway epithelial cells to mitigate the allergic response. In contrast to the effects of LPS treatment, the alarmin high-mobility group protein B1 acts in synergy with polyI:C to promote TSLP and IL33 expression. Our data support part of the hygiene hypothesis in airway epithelia cells in vitro. In addition to therapeutic targeting of TSLP and IL33, local application of non-pathogenic LPS may be a rational strategy to prevent allergies.

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“…More recently, epithelial cells have been shown to produce novel "innate cytokines," TSLP, IL-25, and IL-33, which create a permissive environment for type 2 differentiation of dendritic cells, T cells, and innate lymphoid cells, leading to production of the proasthmatic cytokines IL-4, IL-5, and IL-13. Studies in humans and mice demonstrate that viruses, specifically RV and influenza, can elicit this epithelial cell response (91)(92)(93)(94). RSV infection may also contribute to the development of allergy by breaking immune tolerance to allergens early in life.…”

Section: Biologic Mechanisms Through Which Respiratory Viral Infectiomentioning

confidence: 99%

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

Feldman

Moore

et al. 2015

Am J Respir Crit Care Med

171

172

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A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts.

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Rhinovirus infection in young children is associated with elevated airway TSLP levels

Cited by 45 publications

References 15 publications

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

Lipopolysaccharide Attenuates Induction of Proallergic Cytokines, Thymic Stromal Lymphopoietin, and Interleukin 33 in Respiratory Epithelial Cells Stimulated with PolyI:C and Human Parechovirus

Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma

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